J Cancer 2020; 11(7):1985-1993. doi:10.7150/jca.40002 This issue

Research Paper

Systematic analysis of genetic variants in cancer-testis genes identified two novel lung cancer susceptibility loci in Chinese population

Zhihua Li1*, Jianwei Tang1*, Wei Wen1*, Weibing Wu1, Jun Wang1, Jing Xu1, Yue Yu1, Zhicheng He1, Xianglong Pan1, Haixing Wei1, Yining Zhu1, Shuo Hu1, Jing Cao1, Hongbing Shen2,3, Jun Que1, Wei Wang1, Quan Zhu1✉, Liang Chen1✉

1. Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
2. Department of Epidemiology, Center for Global Health, International Joint Research Center, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
3. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center of Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Li Z, Tang J, Wen W, Wu W, Wang J, Xu J, Yu Y, He Z, Pan X, Wei H, Zhu Y, Hu S, Cao J, Shen H, Que J, Wang W, Zhu Q, Chen L. Systematic analysis of genetic variants in cancer-testis genes identified two novel lung cancer susceptibility loci in Chinese population. J Cancer 2020; 11(7):1985-1993. doi:10.7150/jca.40002. Available from https://www.jcancer.org/v11p1985.htm

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Cancer-testis (CT) genes played important roles in the progression of malignant tumors and were recognized as promising therapeutic targets. However, the roles of genetic variants in CT genes in lung cancer susceptibility have not been well depicted. This study aimed to evaluate the associations between genetic variants in CT genes and lung cancer risk in Chinese population. A total of 22,556 qualified SNPs from 268 lung cancer associated CT genes were initially evaluated based on our previous lung cancer GWAS (Genome-wide association studies) with 2,331 cases and 3,077 controls. As a result, 17 candidate SNPs were further genotyped in 1,056 cases and 1,053 controls using Sequenom platform. Two variants (rs6941653, OPRM1, T > C, screening: OR = 1.24, 95%CI: 1.12-1.38, P = 2.40×10-5; validation: OR = 1.18, 95%CI: 1.01-1.37, P = 0.039 and rs402969, NLRP8, C > T, screening: OR = 1.15, 95%CI: 1.04-1.26, P = 0.006; validation: OR = 1.16, 95%CI: 1.02-1.33, P = 0.028) were identified as novel lung cancer susceptibility variants. Stratification analysis indicated that the effect of rs6941653 was stronger in lung squamous cell carcinoma (OR = 1.36) than that in lung adenocarcinoma (OR = 1.15, I2 = 77%, P = 0.04). Finally, functional annotations, differential gene expression analysis, pathway and gene ontology analyses were performed to suggest the potential functions of our identified variants and genes. In conclusion, this study identified two novel lung cancer risk variants in Chinese population and provided deeper insight into the roles of CT genes in lung tumorigenesis.

Keywords: cancer-testis genes, lung cancer susceptibility, single nucleotide polymorphisms, Chinese population, Sequenom platform